SUMMARY/ABSTRACT Little is known about the role of gut fungi in regulating a healthy gut microflora and in contributing to inflammatory disorders. Most studies of gut microflora focus on commensal bacteria which make up the majority of microbes in the gut. Numerous studies have documented effects of intestinal bacteria on tuning mucosal immunity and in instructing tissue development and repair. Antibiotic use, host genetics, and diet influence the bacterial microbiota and susceptibility to intestinal inflammatory disease. What about fungi? Our overall hypothesis is that intestinal fungal dysbiosis influences the immune system in ways that can increase susceptibility to inflammatory disease and that can be targeted to increase resistance to inflammatory disease. In this renewal proposal, we document that disruption of the ?normal? mycobiome in mice causes increased susceptibility to colitis and to allergic asthma. We propose studies aimed at understanding how antibiotic use, host genetics, and diet influence the intestinal fungal microbiota (?mycobiota?) in the near and long-term. We will characterize how common (Candida and Saccharomyces) and less well-known (Wallemia, Epicoccum) fungi influence susceptibility to intestinal inflammatory disease.